The immunosuppressive tumor microenvironment in hepatocellular carcinoma.
Increasing evidence indicates the immunosuppressive nature of the local environment in tumor. The present study was focused on analyzing the immune status within hepatocellular carcinoma. In contrast to the increasing number of CD4(+) T cells, CD8(+), CD3(-)CD56(+), CD3(+)CD56(+), and gammadeltaT cells were all found to be under-represented in tumor infiltrating lymphocytes. Notably, the relative abundance of CD3(+)CD56(+) cells appeared to be correlated with patient survival. Functional analysis demonstrated that CD4(+) cells in the tumor tended to produce more IL-10 but less IFN-gamma, whereas CD8(+) cells showed impaired capacity for the production of both IFN-gamma and perforin. Consistent with previous reports, we observed a significant increase of Foxp3(+) cells in the tumor tissue. Intriguingly, although over 90% of CD4(+)CD25(high) cells were found to be Foxp3(+), the majority of Foxp3(+) cells were identified in the CD4(+)CD25(medium) and CD4(+)CD25(-) subsets. In support of its role as a negative regulator, CD4(+)CD25(high) cells suppressed the proliferation of CD4(+)CD25(-) cells isolated from the same tissues in an APC dependent manner. In conclusion, the tumor microenvironment of hepatocellular carcinoma is featured by the presence of multiple immunosuppressive factors.
Pang
Yan-Li
YL
Department of Immunology, Peking University Health Science Center, Beijing, People's Republic of China.
Zhang
Hua-Gang
HG
Peng
Ji-Run
JR
Pang
Xue-Wen
XW
Yu
Shu
S
Xing
Qiao
Q
Yu
Xin
X
Gong
Lei
L
Yin
Yan-Hui
YH
Zhang
Yu
Y
Chen
Wei-Feng
WF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D007371:Interferon-gamma